Replacing or repairing damaged or lost tissue is among the most expensive medical therapies and cost billions of dollars a year all over the world. There is an increasing demand for new methods and materials that can be applied in tissue engineering.
The experience of transplanting multiplied stem cells or specific donor stem cells into the human body, e.g. in joints, heart, brain and endocrine organs, has not been successful in showing significant long term survival of the transplanted cells. In a few studies, however, some impact on vascular ingrowth and repair with cell recruitment and minor clinical improvement has been reported.
The most obvious reason for the reported short term effect of transplanted stem cells on local repair (Gazit et al. 2006) is in our opinion that the transplanted cells during their short survival time act as a local cell factory producing a cascade of growth factors and extracellular matrix proteins capable of recruiting progenitor stem cells. Recent studies using colony-stimulating factors to enhance local tissue generation recruiting existing local or circulating stem cells strengthen this hypothesis. It has been demonstrated that the human brain contains cells with stem cell-like properties and an ability to generate new neurons from generator stem cells (Brederlau et al 2004). It has also recently been shown that the combination of transplanting neuroprecursor cells together with single growth factors in injured rat spinal cord in an acute phase will slightly improve the nerve function. The same effect was not seen if the transplantation was carried out after 8 weeks (Karima et al. 2006).
Bio-engineered tissue has been successfully used for replacement purposes in a limited number of clinical applications for example in the treatment of bone defects, diabetic ulcers and for tendon ruptures. The most successful approach has been to select different cell types that exhibit the function and characteristics of the tissue of interest. The best long term results have been reported in the knee for isolated chondral defects using autografts, i.e. chondrocytes cultured in a bioreactor on a scaffold using, for example, a 3-dimensional matrix, a collagen fleece or hyaluronan. However, mincing cartilage and distributing it on a similar matrix in a one-stage procedure without prior culturing gives as good results as with autologous chondrocyte implantation. In both cases a hyaline-like cartilage will be the result. The implant will often integrate poorly with neighbouring cartilage. This almost always gives a scar tissue leaving a cleft, in the area between healthy cartilage and the transplant (Yiling et al 2006).
In WO2002/067762 A2 a muscle polymer construct for bone tissue engineering is described, wherein a bone grafting material comprising a polymer scaffold loaded with bone morphogenetic proteins and populated with muscle cells is prepared to synthesize bone tissue.
In US20050019419 a tissue graft composition comprising liver basement membrane and a method of preparation of this tissue graft composition are described. The graft composition can be implanted to replace or induce the repair of damaged or diseased tissues.
U.S. Pat. No. 6,096,347 describes the use of submucosal tissue of a warm-blooded vertebrate to manufacture a tissue graft composition that induces the formation of endogenous cardiac tissues in vivo upon contact of the cardiac tissues with the manufactured composition.
WO 01/14527 refers to a conditioned medium composition containing skin agents produced from cultured cells of skin and a carrier agent for topical application on the skin.
US 2002/0049422 A1 discloses a topical composition comprising different growth factors.
WO 02/24219 refers to an isolated protein complex comprising a growth factor binding protein, vitronectin and a growth factor, as well as a surgical implant and a skin regeneration medicament comprising said complex.
In view of the prior art there still remains a need to improve the replacing and repairing of damaged or lost tissue within the body of human and animal subjects. The applications of repairing and replacing damaged or lost tissue are extensive and the conditions to be treated are many.
As will be apparent from the following, the present invention is directed to solving such needs.